British Medical Journal
16 March 2013 (Vol 346, Issue 7899)
http://www.bmj.com/content/346/7899

Research
Comparative effect sizes in randomised trials from less developed and more developed countries: meta-epidemiological assessment
Orestis A Panagiotou, research associate1, Despina G Contopoulos-Ioannidis, clinical associate professor23, John P A Ioannidis, director4, C F Rehnborg professor in disease prevention, professor of medicine, and professor of health research and policy5
BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f707 (Published 12 February 2013)
Cite this as: BMJ 2013;346:f707

Abstract
Objective  To compare treatment effects from randomised trials conducted in more developed versus less developed countries.

Design  Meta-epidemiological study.

Data sources C Cochrane Database of Systematic Reviews (August 2012).

Data extraction  Meta-analyses with mortality outcomes including data from at least one randomised trial conducted in a less developed country and one in a more developed country. Relative risk estimates of more versus less developed countries were compared by calculating the relative relative risks for each topic and the summary relative risks across all topics. Similar analyses were performed for the primary binary outcome of each topic.

Results  139 meta-analyses with mortality outcomes were eligible. No nominally significant differences between more developed and less developed countries were found for 128 (92%) meta-analyses. However, differences were beyond chance in 11 (8%) cases, always showing more favourable treatment effects in trials from less developed countries. The summary relative risk was 1.12 (95% confidence interval 1.06 to 1.18; P<0.001; I2=0%), suggesting significantly more favourable mortality effects in trials from less developed countries. Results were similar for meta-analyses with nominally significant treatment effects for mortality (1.15), meta-analyses with recent trials (1.14), and when excluding trials from less developed countries that subsequently became more developed (1.12). For the primary binary outcomes (127 meta-analyses), 20 topics had differences in treatment effects beyond chance (more favourable in less developed countries in 15/20 cases).

Conclusions  Trials from less developed countries in a few cases show significantly more favourable treatment effects than trials in more developed countries and, on average, treatment effects are more favourable in less developed countries. These discrepancies may reflect biases in reporting or study design as well as genuine differences in baseline risk or treatment implementation and should be considers when generalising evidence across different settings.